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J. Biochem, 1994, Vol. 116, No. 4 862-869
© 1994 Japanese Biochemical Society


research-article

Marked Stimulation of Cell Adhesion and Motility by Ladsin, a Laminin-Like Scatter Factor1

Yamato Kikkawa, Makoto Umeda and Kaoru Miyazaki2

Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University 2-120-3 Nakamura-cho, Minami-ku, Yokohama 232

2To whom correspondence should be addressed.

Ladsin is a large cell-adhesive protein with potent cell-scattering activity, which was recently identified in the culture of a malignant human gastric carcinoma cell line [Miyazaki, K. et al. (1993) Proc. Natl. Acad. Set USA 90, 11767–11771]. It is a heterotri-meric protein, containing a 140-kDa subunit similar or identical to the laminin B2t chain. Ladsin is similar to the keratinocyte-derived matrix proteins, "epiligrin" and "kalinin." In the present study, the cell-adhesion and cell-migration activities of ladsin were examined in comparison with those of three cell adhesion proteins, laminin, fibronectin, and vitronectin. Ladsin showed high cell-adhesion activity toward rat liver cell line BRL at concentrations 4–20-times lower than in the case of the other three proteins. In a monolayer culture, ladsin stimulated the migration of BRL cells about 2-times more strongly than the others, as compared at the minimal concentrations required for the maximal cell-adhesion activity. In Boyden chambers, ladsin stimulated both thechemotac-tic and chemokinetic migration of BRL cells. When the effect of anti-integrin antibodies on the adhesion of human fibrosarcoma cell line HT1080 was examined, the adhesion to ladsin was effectively inhibited by both the anti-integrin {alpha}3 and ß1 antibodies, but not the anti-integrin {alpha}6 antibody, indicating that the primary receptor of ladsin is integrin {alpha}3ß1. These results demonstrate that ladsin is a unique extracellular matrix component which may play a major role in cell migration.

1This work was supported by a Grant-in-Aid from the Ministry of Education, Science and Culture, and Special Coordination Funds from the Science and Technology Agency of Japan.


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